The broad goal of this research is to measure the rates at which gases, ions and un-ionized molecules involved in respiratory exchanges move between the red cell interior and environment or tissue cell, in man and animals, in health and in disease. A more distant goal is to determine if any particular step is rate limiting and if this rate can then be used to make measurements of the capillary bed in vivo. A major portion of the work will involve the application of rapid-reaction apparatus, stopped-flow and continuous flow, using PCO2, pH and PO2 electrodes as well as spectrophotometry for analysis, to study fast exchanges of red blood cells. We will (1) measure red cell permeability to ions, particularly HCO minus over 3 and Cl minus; (2) seek evidence for facilitated transport of HCO minus over 3 in the red cell; (3) develop a mathematical description of respiratory exchanges within the blood including ligand interactions with hemoglobin; (4) measure intracellular carbonic anhydrase activity in a variety of conditions and diseases using the exchange of O18 in CO2 with water; (5) seek an explanation for the slow dissociation of HbO2 after the formation of hemoglobin carbamate; (6) determine theta CO for normal blood under different conditions for use in measuring DLCO; (7) investigate variations in hemoglobin charge, anion binding and O2 affinity as a functions of hemoglobin concentrations; (8) apply a combined dye plus O18 venous dilution technique to measure average tissue PO2 in various pathological and physiological conditions; (9) explore the possible physiological implications of a slow plasma pH re-adjustment after gas exchange; (10) investigate the mechanism by which H ion moves out of active cells and its kinetics; and (11) study the pharmacodynamics of carbonic anhydrase. Bibliographic references: Forster, R.E., and E.D. Crandall. Time course of exchanges between red cells and extracellular fluid during CO2 uptake. J. Appl. Physiol. 38:710-718, 1975.